Method of administering upadacitinib to avoid adverse drug interactions and effects

Abstract

The present disclosure is directed to methods for treating immunological diseases and disorders with upadacitinib. The methods include adjusting the dose of upadacitinib in patients with severe renal impairment, in patients concurrently receiving a strong inhibitor of cytochrome P450 3A4 (CYP3A4), and in adult patients 65 years of age and older.

1 . A method of treating a patient concurrently receiving a strong CYP3A4 inhibitor with a therapeutically effective amount of upadacitinib, the method comprising:
 if the recommended daily upadacitinib dose for the patient is 45 mg in the absence of a strong CYP3A4 inhibitor, administering 30 mg to the patient during the time the patient is receiving the strong CYP3A4 inhibitor;   if the recommended daily upadacitinib dose for the patient is 30 mg in the absence of a strong CYP3A4 inhibitor, administering 15 mg to the patient during the time the patient is receiving the strong CYP3A4 inhibitor; and   if the recommended daily upadacitinib dose for the patient is 15 mg in the absence of a strong CYP3A4 inhibitor, administering 15 mg to the patient during the time the patient is receiving the strong CYP3A4 inhibitor.   
     
     
         2 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 45 mg is an adult having moderately to severely active ulcerative colitis, and the daily upadacitinib dose of 30 mg is an induction dose administered for 8 weeks. 
     
     
         3 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 45 mg is an adult having moderately to severely active Crohn's disease, and the daily upadacitinib dose of 30 mg is an induction dose administered for 8 to 16 weeks. 
     
     
         4 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is an adult refractory, severe or extensive ulcerative colitis, and the daily upadacitinib dose of 15 mg is a maintenance dose. 
     
     
         5 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is an adult having refractory, severe or extensive Crohn's disease, and the daily upadacitinib dose of 15 mg is a maintenance dose. 
     
     
         6 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is a pediatric patient 12 years of age and older weighing at least 40 kg having atopic dermatitis that did not achieve adequate response with a daily upadacitinib dose of 15 mg, or an adult less than 65 years of age having atopic dermatitis that did not achieve adequate response with a daily upadacitinib induction dose of 15 mg. 
     
     
         7 . The method of  claim 1 , wherein the patient for whom the recommended daily upadacitinib dose is 15 mg is an adult having moderately to severely active rheumatoid arthritis, an adult having active psoriatic arthritis, an adult or pediatric patient 12 years of age and older having refractory, moderate to severe atopic dermatitis, or an adult having active axial spondyloarthritis. 
     
     
         8 . The method of  claim 1 , wherein the CYP3A4 inhibitor is ketoconazole. 
     
     
         9 . The method of  claim 1 , wherein 400 mg of the ketoconazole is administered once daily for 6 days. 
     
     
         10 . A method of treating a patient concurrently receiving a strong CYP3A4 inhibitor with a therapeutically effective amount of upadacitinib, the method comprising:
 if the recommended daily upadacitinib dose for the patient is 45 mg in the absence of a strong CYP3A4 inhibitor, administering 30 mg to the patient during the time the patient is receiving the strong CYP3A4 inhibitor; or   if the recommended daily upadacitinib dose for the patient is 30 mg in the absence of a strong CYP3A4 inhibitor, administering 15 mg to the patient during the time the patient is receiving the strong CYP3A4 inhibitor.   
     
     
         11 . The method of  claim 10 , wherein the patient is an adult having moderately to severely active ulcerative colitis and the recommended daily upadacitinib dose for the patient is 45 mg, the method comprising administering an once daily upadacitinib induction dose of 30 mg for 8 weeks. 
     
     
         12 . The method of  claim 10 , wherein the patient is an adult having moderately to severely active Crohn's disease and the recommended daily upadacitinib dose for the patient is 45 mg, the method comprising administering a once daily upadacitinib induction dose of 30 mg for 8 to 16 weeks. 
     
     
         13 . The method of  claim 10 , wherein the patient is an adult having refractory, severe or extensive ulcerative colitis and the recommended daily upadacitinib dose for the patient is 30 mg, the method comprising administering a once daily upadacitinib maintenance dose of 15 mg. 
     
     
         14 . The method of  claim 10 , wherein the patient is an adult having refractory, severe or extensive Crohn's disease and the recommended daily upadacitinib dose of 30 mg, the method comprising administering a once daily upadacitinib maintenance dose of 15 mg. 
     
     
         15 . The method of  claim 10 , wherein the patient is a pediatric patient 12 years of age and older weighing at least 40 kg having atopic dermatitis that did not achieve adequate response with a daily upadacitinib dose of 15 mg, or an adult less than 65 years of age having atopic dermatitis that did not achieve adequate response with a daily upadacitinib induction dose of 15 mg, the method comprising administering a once daily upadacitinib dose of 15 mg. 
     
     
         16 . The method of  claim 10 , wherein the CYP3A4 inhibitor is ketoconazole. 
     
     
         17 . The method of  claim 10 , wherein 400 mg of the ketoconazole is administered once daily for 6 days. 
     
     
         18 . A method of treating patients having severe renal impairment with a therapeutically effective amount of upadacitinib, the method comprising:
 if the recommended daily upadacitinib dose for the patient is 45 mg in the absence of severe renal impairment, administering 30 mg to the patient during the time the patient has severe renal impairment;   if the recommended daily upadacitinib dose for the patient is 30 mg in the absence of severe renal impairment, administering 15 mg to the patient during the time the patient has severe renal impairment; and   if the recommended daily upadacitinib dose for the patient is 15 mg in the absence of severe renal impairment, administering 15 mg to the patient during the time the patient has severe renal impairment.   
     
     
         19 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 45 mg is an adult having moderately to severely active ulcerative colitis, and the daily upadacitinib dose of 30 mg is an induction dose administered for 8 weeks. 
     
     
         20 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 45 mg is an adult having moderately to severely active Crohn's disease, and the daily upadacitinib dose of 30 mg is an induction dose administered for 8 to 16 weeks. 
     
     
         21 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is an adult refractory, severe or extensive ulcerative colitis, and the daily upadacitinib dose of 15 mg is a maintenance dose. 
     
     
         22 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is an adult having refractory, severe or extensive Crohn's disease, and the daily upadacitinib dose of 15 mg is a maintenance dose. 
     
     
         23 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 30 mg is a pediatric patient 12 years of age and older weighing at least 40 kg having atopic dermatitis that did not achieve adequate response with a daily upadacitinib dose of 15 mg, or an adult less than 65 years of age having atopic dermatitis that did not achieve adequate response with a daily upadacitinib induction dose of 15 mg. 
     
     
         24 . The method of  claim 18 , wherein the patient for whom the recommended daily upadacitinib dose is 15 mg is an adult having moderately to severely active rheumatoid arthritis, an adult having active psoriatic arthritis, an adult or pediatric patient 12 years of age and older having refractory, moderate to severe atopic dermatitis, or an adult having active axial spondyloarthritis. 
     
     
         25 . A method of treating a patient having severe renal impairment with a therapeutically effective amount of upadacitinib, the method comprising:
 if the recommended daily upadacitinib dose for the patient is 45 mg in the absence of a severe renal impairment, administering 30 mg to the patient during the time the patient has severe renal impairment; or   if the recommended daily upadacitinib dose for the patient is 30 mg in the absence of severe renal impairment, administering 15 mg to the patient during the time the patient has severe renal impairment.   
     
     
         26 . The method of  claim 25 , wherein the patient is an adult having moderately to severely active ulcerative colitis and the recommended daily upadacitinib dose for the patient is 45 mg, the method comprising administering a once daily upadacitinib induction dose of 30 mg for 8 weeks. 
     
     
         27 . The method of  claim 25 , wherein the patient is an adult having moderately to severely active Crohn's disease and the recommended daily upadacitinib dose for the patient is 45 mg, the method comprising administering a once daily upadacitinib induction dose of 30 mg for 8 to 16 weeks. 
     
     
         28 . The method of  claim 25 , wherein the patient is an adult having refractory, severe or extensive ulcerative colitis and the recommended daily upadacitinib dose for the patient is 30 mg, the method comprising administering a once daily upadacitinib maintenance dose of 15 mg. 
     
     
         29 . The method of  claim 25 , wherein the patient is an adult having refractory, severe or extensive Crohn's disease and the recommended daily upadacitinib dose of 30 mg, the method comprising administering a once daily upadacitinib maintenance dose of 15 mg. 
     
     
         30 . The method of  claim 25 , wherein the patient is a pediatric patient 12 years of age and older weighing at least 40 kg having atopic dermatitis that did not achieve adequate response with a daily upadacitinib dose of 15 mg, or an adult less than 65 years of age having atopic dermatitis that did not achieve adequate response with a daily upadacitinib induction dose of 15 mg, the method comprising administering a once daily upadacitinib dose of 15 mg.